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Abstract Background Isolated syndactyly in cattle, also known as mulefoot, is inherited as an autosomal recessive trait with variable penetrance in different cattle breeds. Recently, two independent mutations in the bovine LRP4 gene have been reported as the primary cause of syndactyly in the Holstein and Angus cattle breeds. Results We confirmed the previously described LRP4 exon 33 two nucleotide substitution in most of the affected Holstein calves and revealed additional evidence for allelic heterogeneity by the identification of four new LRP4 non-synonymous point mutations co-segregating in Holstein, German Simmental and Simmental-Charolais families. Conclusion We confirmed a significant role of LRP4 mutations in the pathogenesis of congenital syndactyly in cattle. The newly detected missense mutations in the LRP4 gene represent independent mutations affecting different conserved protein domains. However, the four newly described LRP4 mutations do still not explain all analyzed cases of syndactyly.

Source analysis of magnetoencephalography (MEG) data requires the computation of the magnetic fields induced by current sources in the brain. This so-called MEG forward problem includes an accurate estimation of the volume conduction effects in the human head. Here, we introduce the Cut finite element method (CutFEM) for the MEG forward problem. CutFEM's meshing process imposes fewer restrictions on tissue anatomy than tetrahedral meshes while being able to mesh curved geometries contrary to hexahedral meshing. To evaluate the new approach, we compare CutFEM with a boundary element method (BEM) that distinguishes three tissue compartments and a 6-compartment hexahedral FEM in an n = 19 group study of somatosensory evoked fields (SEF). The neural generators of the 20 ms post-stimulus SEF components (M20) are reconstructed using both an unregularized and a regularized inversion approach. Changing the forward model resulted in reconstruction differences of about 1 centimeter in location and considerable differences in orientation. The tested 6-compartment FEM approaches significantly increase the goodness of fit to the measured data compared with the 3-compartment BEM. They also demonstrate higher quasi-radial contributions for sources below the gyral crowns. Furthermore, CutFEM improves source separability compared with both other approaches. We conclude that head models with 6 compartments rather than 3 and the new CutFEM approach are valuable additions to MEG source reconstruction, in particular for sources that are predominantly radial., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

The hard tick Ixodes ricinus transmits a variety of zoonotic pathogens, including Babesia divergens , the most common cause of bovine babesiosis in northern Europe. In endemic areas, cattle are rarely clinically affected, as animals up to the age of nine months are resistant against relevant clinical disease and develop protective premunity. However, outbreaks in immunologically naïve herds may lead to considerable losses. Such an outbreak with a high mortality rate occurred in 2018 on a northern German beef production farm, as previously reported. The present study provides an update on the epidemiological situation and management strategy of the farm. In spring 2022, blood samples were taken from 46 animals for PCR and serological testing before pasture turnout. Although no clinical cases had been noticed since 2019, B. divergens DNA was detected by quantitative real-time PCR (qPCR), followed by amplification and sequencing of the 18S rRNA gene, in 6.5% (3/46) of cattle blood samples. Presence of anti- B. divergens antibodies was confirmed in 26.1% (12/46) of animals, while further 10.9% (5/46) had a borderline antibody titre. The antibody status of 23 of these animals had already been determined in 2018 and/or 2020, revealing fluctuating titre patterns indicative of repeated pathogen exposure. Moreover, 457 questing I. ricinus specimens collected on the farm's pastures and 83 I. ricinus specimens detached from cattle were screened for Babesia spp. DNA by qPCR, followed by 18S rDNA amplification and sequencing. Endemisation of B. divergens was confirmed by 0.9% (4/457) positive questing I. ricinus , while the ticks detached from cattle were Babesia -negative. The farm's management strategy includes annual metaphylactic treatment with imidocarb dipropionate during the main tick exposure period in spring. However, the antibody titre fluctuations and the persistent infections at the end of the housing period indicate that the absence of clinical disease is primarily due to a rising level of premunity. Metaphylactic treatment with imidocarb seems to be a suitable management option to protect newly acquired immunologically naïve animals. The endemisation of B. divergens is also of public health significance, as the pastures are located close to a tourist destination in a popular hiking area., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dieter Barutzki acted as Managing Director of the diagnostic Tierärztliches Labor Freiburg GmbH and had research collaborations with veterinary pharmaceutical companies; Christina Strube has repeatedly lectured for and acted as a consultant for diagnostic and (veterinary) pharmaceutical companies and has previous and ongoing research collaborations with various diagnostic and (veterinary) pharmaceutical companies. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Source analysis of Electroencephalography (EEG) data requires the computation of the scalp potential induced by current sources in the brain. This so-called EEG forward problem is based on an accurate estimation of the volume conduction effects in the human head, represented by a partial differential equation which can be solved using the finite element method (FEM). FEM offers flexibility when modeling anisotropic tissue conductivities but requires a volumetric discretization, a mesh, of the head domain. Structured hexahedral meshes are easy to create in an automatic fashion, while tetrahedral meshes are better suited to model curved geometries. Tetrahedral meshes, thus, offer better accuracy but are more difficult to create., Methods: We introduce CutFEM for EEG forward simulations to integrate the strengths of hexahedra and tetrahedra. It belongs to the family of unfitted finite element methods, decoupling mesh and geometry representation. Following a description of the method, we will employ CutFEM in both controlled spherical scenarios and the reconstruction of somatosensory-evoked potentials., Results: CutFEM outperforms competing FEM approaches with regard to numerical accuracy, memory consumption, and computational speed while being able to mesh arbitrarily touching compartments., Discussion: CutFEM balances numerical accuracy, computational efficiency, and a smooth approximation of complex geometries that has previously not been available in FEM-based EEG forward modeling., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Erdbrügger, Westhoff, Höltershinken, Radecke, Buschermöhle, Buyx, Wallois, Pursiainen, Gross, Lencer, Engwer and Wolters.)

Human brain activity generates scalp potentials (electroencephalography - EEG), intracranial potentials (iEEG), and external magnetic fields (magnetoencephalography - MEG). These electrophysiology (e-phys) signals can often be measured simultaneously for research and clinical applications. The forward problem involves modeling these signals at their sensors for a given equivalent current dipole configuration within the brain. While earlier researchers modeled the head as a simple set of isotropic spheres, today's magnetic resonance imaging (MRI) data allow for a detailed anatomic description of brain structures and anisotropic characterization of tissue conductivities. We present a complete pipeline, integrated into the Brainstorm software, that allows users to automatically generate an individual and accurate head model based on the subject's MRI and calculate the electromagnetic forward solution using the finite element method (FEM). The head model generation is performed by integrating the latest tools for MRI segmentation and FEM mesh generation. The final head model comprises the five main compartments: white-matter, gray-matter, CSF, skull, and scalp. The anisotropic brain conductivity model is based on the effective medium approach (EMA), which estimates anisotropic conductivity tensors from diffusion-weighted imaging (DWI) data. The FEM electromagnetic forward solution is obtained through the DUNEuro library, integrated into Brainstorm, and accessible with either a user-friendly graphical interface or scripting. With tutorials and example data sets available in an open-source format on the Brainstorm website, this integrated pipeline provides access to advanced FEM tools for electromagnetic modeling to a broader neuroscience community., Competing Interests: Declaration of Competing Interest The authors declare that they have no known financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Bovine babesiosis, caused by Babesia divergens , is in general a rare disease in Europe. Nonetheless, local outbreaks can cause severe economic damage, and postmortem identification represents a diagnostic challenge. During a recent outbreak in May 2018 in northern Germany, 21 animals of a herd of 150 cattle died within 40 days having had clinical signs of fever and hemoglobinuria. Gross examination of 4 of the 21 deceased animals revealed a tick infestation, jaundice, and dark brown staining of urine and kidneys. Histologically, there were iron-positive deposits, hyperplasia of the red pulp of the spleen, and centrilobular necrosis of hepatocytes. In several locations, small basophilic granules suggestive of intraerythrocytic parasites were visible in hematoxylin-eosin- and Giemsa-stained sections. Peripheral blood smears from a living cow from the herd and polymerase chain reaction (PCR) of feeding ticks revealed B. divergens infection. In situ hybridization (ISH) was applied on formalin-fixed, paraffin-embedded (FFPE) tissue of the necropsied cattle to confirm babesiosis in these animals postmortem. Digoxigenin-labeled DNA probes were generated based on a specific nucleotide sequence for B. divergens , obtained by PCR and sequencing of DNA isolates from infected Ixodes ricinus ticks from deceased cattle. ISH using these probes allowed postmortem diagnosis of B. divergens infection in routinely fixed FFPE tissues.

Babesia divergens , transmitted by the tick Ixodes ricinus , is the most common cause of bovine babesiosis in northern Europe and plays a role as a zoonotic pathogen. However, several studies have indicated a decline of B. divergens prevalence in Europe during the last decades. Here, we investigate the epidemiology of bovine babesiosis on a beef production farm in northern Germany, which had not been affected by babesiosis until an initial outbreak in 2018. In June 2018, 21 adult cattle died, showing classical symptoms of babesiosis. Babesia divergens merozoites were detected in blood smears of clinically affected animals and the species was confirmed by PCR and sequencing of a part of the 18S rRNA gene. In 2018, screening of the farm's entire stock by PCR revealed that Babesia -positive animals were present in only one of five herds grazing on different pastures. In the following year, further babesiosis cases occurred in multiple herds. In March 2020, 95 cattle were tested for anti- B. divergens antibodies and 36 of them (37.89%) had positive titres. To investigate the local Babesia prevalence in ticks, 1,430 questing I. ricinus ticks (555 larvae, 648 nymphs, 227 adults) were collected on the farm's pastures and subjected to PCR for Babesia detection. Babesia divergens DNA could not be detected, but Babesia microti showed an overall prevalence of 0.49% (7/1,430; 0.88% [2/227] of adult ticks, 0.77% [5/648] of nymphs, 0.00% [0/555] of larvae). Babesia venatorum was detected in 0.42% (6/1,430) of ticks (0.44% [1/227] of adult ticks, 0.77% [5/648] of nymphs, 0.00% [0/555] of larvae) and B. capreoli in 0.07% (1/1,430) of ticks (0.00% [0/227] of adult ticks, 0.15% [1/648] of nymphs, 0.00% [0/555] of larvae). Despite the fact that no B. divergens -positive ticks were found, the collected data suggest a geographical spread of the pathogen on the farm. Bovine babesiosis remains a disease of veterinary importance in Europe and may cause considerable economic losses when (re-)emerging in non-endemic areas, especially as awareness for the disease among veterinarians and farmers declines., (Copyright © 2020 Springer, Höltershinken, Lienhart, Ermel, Rehage, Hülskötter, Lehmbecker, Wohlsein, Barutzki, Gietl, Baumgärtner, Hoedemaker and Strube.)

Pancreatic exocrine insufficiency (PEI) is a disease of diverse aetiology-e.g., majority of patients suffering from cystic fibrosis (CF) show PEI congenitally. Malnutrition and malabsorption of nutrients impair growth and nutritional status. As reduced fat digestion leads to a deficiency of fat-soluble vitamins the supplementation is standard, but absorption is a critical point in PEI-patients. The pancreatic duct ligated (PL) pig is an established model for PEI in humans and has been proven to be a suitable model to compare different vitamin additives for supplementation. In a former study, PEI caused distinct growth retardation in young piglets, but did not affect growth in older ones. Our study hypothesised that this age-dependent effect is caused by exhausted body reserves of fat-soluble vitamins and, therefore, extra supply reduces growth retardation. PEI was induced by PL at the age of seven (PL-7) or 16 weeks (PL-16). Controls (C) underwent a sham surgery. Some PL-7 pigs (PL-7 + Vit) were fed a special vitamin additive. PEI reduced the mean final body weight (kg) at 26 weeks of age significantly with lower effect in PL-16-pigs (C:117; PL-7:49.5; PL-7 + Vit:77.1; PL-16:96.4). Extra vitamin supply resulted in an increased growth and normalised serum concentration of alpha-tocopherol, underlining the importance of special supplementation in PEI-patients., Competing Interests: The authors declare no conflict of interest.

A female calf of the breed German Holstein (GH) was spontaneously born on July 28, 2013 which was 35 days before the expected term of birth. The dam was a heifer when she got pregnant from the first insemination on November 23, 2012. Calving was without complications. The calf was fully viable and without visible anomalies. We assume that the calf was fully mature at the termination of the pregnancy. Growth rate after the second month of life was comparable to calves born in the same herd after normal length of gestation. The sire of this preterm calf was a GH-bull used for artificial insemination. This bull had already sired 151 daughters. For this bull, preterm calvings were not yet reported. The dam was a heifer, and neither external influences on this dam or in the herd could be identified that could have induced this premature calving. In the herd, no further premature calvings were observed or reasons associated with a preterm calving were found. In this exceptional case, however, gestation length was 248 days and the prematurely born calf survived without any signs of debility, organ defects and respiratory distress.

Human patients suffering from exocrine pancreatic insufficiency (EPI) are susceptible to deficiencies in fat-soluble vitamins. In children with cystic fibrosis, EPI is common and aspects of sufficient vitamin supply are of special interest. The aim of this study was to determine the best application form to maintain vitamin A and E levels in the physiological range in growing pigs with EPI (induced by pancreatic duct ligation) as a model for children. The pancreatic duct was ligated (PL) in twelve 8-wk-old pigs; 4 sham-operated pigs served as controls (Con). Pigs (n = 16) were individually housed and fed a diet containing 13,393 IU vitamin A and 122 mg vitamin E/kg DM. The PL pigs (n = 12) were divided into 3 groups (n = 4) 2 wk after surgery: PL-0, without extra vitamin supply; PL+ORAL, 90,000 IU vitamin A and 600 mg vitamin E/kg of DM plus emulsifier E 484 added to the diet; and PL+IM, intramuscular injection of vitamin A (5,250 IU) and vitamin E [aqueous; 3.15 mg/(kg BW · wk)] plus 700 mg vitamin E (oily)/(animal · wk). All PL pigs were supplemented with the pancrelipase Creon (19.8 g = 1,048,727 IU lipase/kg feed) beginning 2 wk after ligation of the pancreatic duct. Pigs were euthanized at 16 wk of age. Tocopherol levels (mg/kg DM) in liver were reduced (P ≤ 0.005) in PL-0 and PL+IM (6.91 and 8.61, respectively) whereas PL+ORAL did not differ from Con (27.4 and 25.8, respectively; P ≥ 0.77). Compared to control pigs (241 ± 14.1 mg vitamin A/kg DM of liver), the concentration of vitamin A (mg/kg DM) in liver was lower (P < 0.003) in PL-0 (136 ± 18.5) but higher (P < 0.003) in PL+ORAL (375 ± 50.0). In the group PL+IM a high individual variation was observed (288 ± 142 mg vitamin A/kg DM of liver). Extra dietary supply of high doses of vitamin A and E with an efficient emulsifier was adequate to maintain vitamin A and E in liver tissue within reference values. The present data underline the need for extra supplementation of vitamin A and E in juvenile patients with EPI and indicate that oral application is suitable.